Advancements in mRNA – an approach to COVID-19 Vaccines

Article No.  392

9 November 2020

 

 

 

For some people, the 9 November 2020 release of new information from Pfizer and BioNTech on the progress of their COVID-19 vaccine candidate triggered vague memories of ‘mRNA’ and the body’s immune system discussed in biology class. This approach to creating a COVID-19 vaccine candidate continued with 16 November news of positive interim data from Moderna regarding their Phase 3 trial of mRNA-1273. Perhaps you experienced the head-scratching moment similar to many individuals, “Messenger RNA. I remember the term mRNA from my university days, but I’m foggy on the particulars.”

 

Let’s clear back the mists of time, and present a quick snapshot of what mRNA is, how it affects the immune system, and how an mRNA vaccine candidate might fit into the context of COVID-19. By no means a comprehensive overview of mRNA, COVID-19, or vaccine candidates against SARS-CoV-2 infection, we present an overview of basic information about mRNA technology and its utilization as a vaccine approach.

 

There remain a few basic matters to consider. Vaccines may prevent disease, but drug discovery for COVID-19 therapeutic drug options must continue so that effective treatments are available for patients battling SARS-CoV-2 infections. Interim data from clinical trials may be positive – yet promising or not, results still need to undergo the rigors of various verification and validation processes. Vaccine effectiveness isn’t the same as vaccine efficacy (McNeil S. Canadian Ctr for Vaccinology, WHO). Likely there are many other aspects to clarify and expound upon concerning potential COVID-19 issues for vaccine candidates. Practical considerations regarding affordability and accessibility play a role, as do matters such as ramping up manufacturing/productions and parameters for vaccine storage and distribution.

 

As of 9 November 2020 there are 282 entries on ClinicalTrials.gov using the search terms ‘COVID-19’ and ‘Vaccine’, which can be viewed by clicking HERE.  That does not include all potential vaccine studies listed on other networks and around the world.  As such, we suggest the World Health Organization’s comprehensive information, on their WHO COVID-19 Vaccines resource Q & A page. This thumbnail sketch from the aHUS Alliance is intended simply to provide a bit of background to current news regarding advancement of mRNA as an approach to COVID-19 vaccines.

 

What are some details about the 9 Nov 2020 news from Pfizer & BioNTech about their vaccine?

 

News of positive data regarding a COVID-19 vaccine was announced by drug companies Pfizer and BioNTech on 9 Nov 2020. Viewed by most as a key milestone in development of an effective vaccine to halt spread of the current world pandemic, data from phase 3 clinical trial of BNT162b2 looks promising.

A few main points from this 9 Nov 2020 press release were as follows. In a study population of over 43,000 people, the Pfizer/BioNTech press release noted their vaccine was 90% effective in preventing COVID-19 in clinical trial participants, with the stated protection level achieved within 28 days after the first dose of its 2-dose schedule.

Read the full press release from Pfizer & BioNTech (9 Nov 2020, 6:45 am ET)

 

What are some details about the 16 Nov 2020 news from Moderna about their vaccine?

Moderna released the 1st interim set of data from their Phase 3 COVE study of the company’s COVID-19 vaccine candidate, mRNA-1273, which indicated a vaccine efficacy of 94.5%. Moderna will submit an ‘Emergency Use Authorization’ to the US FDA in the coming weeks.

Like the 2 dose injection noted by Pfizer/BioNTech COVID-19 vaccine (9 Nov), the Moderna vaccine candidate utilizes messenger RNA to fight the SARScoV2 viral infection. Moderna’s vaccine is reported to require less special storage/handling conditions to ease distribution of the vaccine, with 30 day ‘shelf’ life.  Unlike Pfizer/BioNTech, Moderna had not yet applied for EUA authorization prior to its press release.

FMI:  Moderna (corporate site, IR)

More Details:  BusinessWire (press release)  (16 Nov, 6:56 am ET)

 

On the concept of a vaccine- how does that prevent disease?

It’s difficult to sort through material presented by opposing viewpoints on vaccination in general, let alone companies with a financial incentive to bring a new vaccine to market. Information about COVID-19 updates at a rapid pace, and much of it contains references to antibodies, proteins and other scientific terms.

 

This brief animated video (2 mins, 27 sec) provides a starting point for context, as it gives a simple explanation of how vaccines work  in general. Note: This intentionally is a pre-pandemic video.

 

How do vaccines work?

 

 

 

An animated video which explains how part of the immune system works, the Complement System. With over 30 proteins involved in a complex process, this video explains the functioning of our body’s  defense network to include antibodies as the ‘tools’ which activate the complement system.

Tiny Bombs in Your Blood

 

 

After viewing these two videos, you’ll have a basic background which will enable you to branch out into 2 more topics relative to COVID-19 vaccines – thrombotic microagiopathy and the inflammation process.  FMI and articles on these and other topics: Visit our aHUS Alliance Resource Page

 

What is mRNA & how does it work?

Let’s check in with an explanation from a source with scientific expertise. From the University of Cambridge, on the webpage titled RNA Vaccines: an Introduction

“Unlike a normal vaccine, RNA vaccines work by introducing an mRNA sequence (the molecule which tells cells what to build) which is coded for a disease specific antigen, once produced within the body, the antigen is recognised by the immune system, preparing it to fight the real thing”

“RNA vaccines are faster and cheaper to produce than traditional vaccines, and a RNA based vaccine is also safer for the patient, as they are not produced using infectious elements”

See also – 17 Mar 2020 (Cambridge University UK article)  Cambridge research team working towards vaccine against COVID-19

 

Are there other companies with COVID-19 vaccines in development which also use mRNA technology? 

Moderna is a company focused on creating transformational medicines for human health and diseases by utilizing messenger RNA  to improve how medicines are discovered, developed and manufactured. Moderna has a COVID-19 vaccine candidate in its pipeline, which includes 3 major areas:  Infectious Diseases, Immuno-Oncology, and Rare Diseases.

From a subpage on the Moderna corporate website with this heading: The Science and Fundamentals ofmRNA Technology

“What does mRNA do? mRNA produces instructions to make proteins that may treat or prevent disease.” Continuing to further elaborate, “mRNA medicines aren’t small molecules, like traditional pharmaceuticals. And they aren’t traditional biologics (recombinant proteins and monoclonal antibodies) – which were the genesis of the biotech industry. Instead, mRNA medicines are sets of instructions. And these instructions direct cells in the body to make proteins to prevent or fight disease.”

Info & Links on Moderna’s COVID-19 vaccine candidate mRNA-1273 

Key Milestones (Moderna):  an overview by Moderna on their progress to fight COVID-19

Clinical Trial, Study Name: Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19.  Clinical Trial ID:  NCT04470427

Note: Other COVID-19 vaccine candidates which utilize mRNA & have entered into clinical trials (listed on ClinicalTrials.gov, as of 9 Nov 2020) are:

Clinical Trial ID:  NCT04566276 ChulaCov19 mRNA

Clinical Trial ID: NCT04515147  CVnCoV (CVnCoV 6 μg and 8 μg)

 

 

Additional Assets

aHUS Alliance:   A COVID-19 Resource Page for our Community

This page contains public information about COVID-19, as well as articles & research about the coronavirus which are of high interest to those interested in thrombotic microangiopathy, complement, and the rare disease atypical HUS.

 

Atypical HUS – 2020 Therapeutic Drug Landscape

A look at drug discovery, clinical trials, and market conditions regarding orphan drugs for the aHUS community.  Includes research into genetics and thrombotic microangiopathy, along with a pharma pipeline chart that contains links to complement inhibitors, biosimilars, and drug R & D issues for stakeholders in this rare disease space.

 

The aHUS Alliance provides independent and objective information of interest to our rare disease community – it does not endorse nor promote medical treatments for COVID-19 or atypical HUS. Our articles target specialized segments of information, and do not portray comprehensive outlooks nor medical advice.

Contact your local and/or governmental healthcare agencies for current updates and COVID-19 status for your region.

L Burke (9 Nov 2020)